Methods for stabilizing liquid nutritional products and products so stabilized

ABSTRACT

Nutritional solutions and methods of making same are disclosed. The solutions include protein, lipid, and a carbohydrate source including high amylose starch and guar gum.

BACKGROUND OF THE INVENTION

The present invention relates generally to the treatment of patients andproducts or treating patients. More specifically, the present inventionrelates to enteral solutions or providing nutritional support topatients.

It is of course known to feed patients, requiring nutrition in ahospital or other health care setting (including a home), with enteralor parenteral nutrition solutions. Parenteral nutrition solutionsinclude solutions that are infused intravenously into the patientthrough an IV system. Enteral products include products that are fedinto a patient's gastrointestinal system typically through a nasogastricfeeding tube.

There are a variety of different products that have been designed toprovide enteral nutritional support to a patient. Some of these productsare designed to provide all necessary nutrients. On the other hand, anumber of the enteral products can also be used as supplements to anormal diet. Some of these products are directed to specific diseasestates while other products are more generic and broad based forproviding nutritional support to patients who cannot obtain necessarynutrients through traditional means of eating food.

Depending on the indication of the enteral solution, the formulation maychange. For example, certain patient populations may require increasedprotein levels. Likewise, certain patient populations may requirehydrolyzed or non intact protein.

Nutritional enteral products include: Glytrol®; NutriHep®; NutriVent®;Probalance®; RenalCal®; Crucial®; Peptamen®; Peptamen VHP®; NuBasics®;NuBasics VHP®; Entrition®; Nutren®; Reabliang; Reablian HN®; Replete®;Travasor®; Peptamen Jr.®; and Elementra®, all available from NestléClinical Nutrition, Deerfield, Ill. A number of other manufacturers sellenteral nutrition products including Ross Laboratories a division ofAbbott Laboratories, Mead Johnson, and Novartis.

In certain enteral products serum separation has been observed. Thisphysical instability reduces the product's elegance. Further, it maycreate an adverse impression in the minds of some consumers regardingthe product's quality and acceptability, even though such serumseparation does not adversely affect the quality or efficacy of theproduct.

There is therefore a need for improving the stability of at leastcertain enteral solutions.

SUMMARY OF THE INVENTION

The present invention provides methods for stabilizing nutritionalproducts including enteral solutions. Additionally, the presentinvention provides solutions so stabilized.

To this end, the present invention provides an enteral formulacomprising a protein source, a lipid source, and carbohydrates includinghigh amylose starch and guar gum.

In an embodiment, the protein source comprises approximately 10% toabout 25% of the total calories.

In an embodiment, the lipid source comprises approximately 25% to about50% of the total calories.

In an embodiment, carbohydrates comprise approximately 40% to about 60%of the total calories.

Preferably, the high amylose starch comprises at least approximately 50%amylose.

In an embodiment, high amylose starch and guar gum as a total compriseapproximately 2.25% to about 7.5% of the total caloric content.

In an embodiment, high amylose starch comprises approximately 2% toabout 6.5% of the total caloric content.

In an embodiment, the product includes xanthan.

In an embodiment, guar gum comprises 0.25% to about 1.0% of the totalcaloric content.

In an embodiment, the weight ratio of high amylose starch to guar gum isapproximately 2.5:1 to 16:1.

In an embodiment, the product includes carrageenan.

In another embodiment the present invention provides an enteral productcomprising a hydrolyzed whey protein source, a source of lipids, and asufficient amount of a stabilizer to prevent serum separation, thestabilizer including high amylose starch and guar gum.

In an embodiment, the protein source comprises approximately 10% toabout 25% of the total calories.

In an embodiment, the lipid source comprises approximately 25% to about50% of the total calories.

In an embodiment, high amylose starch and guar gum as a total compriseapproximately 2.25% to about 7.50% of the total caloric content.

In an embodiment, high amylose starch comprises approximately 2.0% toabout 6.5% of the total caloric content.

In an embodiment, guar gum comprises 0.25% to about 1.0% of the totalcaloric content.

In an embodiment, the weight ratio of high amylose starch to guar gum isapproximately 2.5:1 to 16:1.

In an embodiment, the source of lipids includes medium and long chaintriglycerides.

In an embodiment, the product at 1500 Kcal provides at least 100% of theU.S. RDA of vitamins and minerals.

In an embodiment, the product has a caloric content of approximately 1.0Kcal/ml.

In yet a further embodiment of the present invention, a method ofstabilizing an enteral solution is provided. The method comprises thestep of adding to an enteral solution a stabilizing amount of highamylose starch and guar gum.

Accordingly, an advantage of the present intention is to providenutritional products including enteral solutions having greaterstability.

A further advantage of the present invention is to provide a stabilizersystem for nutritional products.

Still further, an advantage of the present invention is to providenutritional products that have improved compatibility of ingredients,especially starches and gums.

Further, an advantage of the present invention is to provide an enteralsolution including hydrolyzed whey protein having a stabilizingcombination of starch and gum.

Moreover, an advantage of the present invention is to provide methods ofstabilizing enteral solutions.

Additionally, an advantage of the present invention is to provideimproved enteral solutions.

Furthermore, an advantage of the present invention is to substantiallyreduce if not eliminate serum separation in enteral products.

Another advantage of the present invention is to provide a method forstabilizing starch and gum combinations.

Additional features and advantages of the present invention aredescribed in, and will be apparent from, the detailed description of thepresently preferred embodiments and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates graphically the effect of starch and gum on viscosityand sediment pursuant to Example No. 1.

FIG. 2 illustrates graphically viscosity of products during storagepursuant to Example No. 1.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

The present invention provides methods for stabilizing nutritionalproducts including enteral solutions. Additionally, the presentinvention provides nutritional products including enteral solutions sostabilized.

There has been observed, in certain enteral solutions, serum separation.It has been found, during stability studies, that serum separation inmany enteral products containing hydrolyzed protein is due to the starchand gum formulation. For example, in the Nestlé product Peptamen®,polysaccharides and guar gum are used in the formula. Specifically, thepolysaccharide is Melojel starch. Peptamen® has been observed in certaincircumstances to suffer from serum separation. It was surprisinglydiscovered that the separation can be eliminated by providing adifferent starch and gum combination.

In this regard, it was surprisingly found that the stability of at leastcertain enteral products can be improved by providing a stabilizingcombination of starch and gum. This starch and gum combination can beadded to the product without requiring any additional label changeswhile at the same time eliminating any possible serum separation.

Specifically, it was discovered that the use of high amylose starch andguar gum stabilizes enteral products, especially those containinghydrolyzed protein. Preferably, the high amylose starch comprises atleast approximately 50% amylose, and most preferably approximately 70%amylose. Preferably, the high amylose starch and guar gum as acombination comprises approximately 2.25% to about 7.5% of the caloriccontent of the product. Preferably the weight ratio of high amylosestarch to guar gum is approximately 2.5:1 to 16:1; and more preferablyapproximately 8:1 to about 12:1. Preferably high amylose starchcomprises approximately 2.0% to 6.5% of the caloric content of theproduct. Preferably guar gum comprises approximately 0.25% to about 1.0%of the caloric content of the product.

The product will include in addition to the stabilizing system of highamylose starch and guar gum a protein source, a lipid source, vitaminsand minerals. Preferably the protein source will comprise approximately10% to about 25%, and more preferably approximately 12% to about 20%, ofthe caloric content of the product. Preferably, the protein ishydrolyzed protein such as hydrolyzed whey or hydrolyzed casein.Preferably, the lipid source will comprise approximately 25% to about50%, and more preferably approximately 30% to about 40%, of the caloriccontent of the product. Preferably, the lipids are a mixture of longchain triglycerides (LCTS) and medium chain triglycerides (MCTS).Preferably the carbohydrate source will comprise approximately 40% toabout 60%, and more preferably approximately 45% to 55%, of the caloriccontent of the product. In a preferred embodiment, the product willprovide at least 100% of the U.S. RDA of vitamins and minerals in 1500Kcal of product (1500 mls).

By way of example, and not limitation, an example of the presentinvention is as follows:

Nutrient Composition Amount % U.S. RDA* Protein 10 g ** Carbohydrate***31.8 g 22 Fat**** 9.8 g ** Water 220 ml ** Vitamin A 1000 I.U. 20Vitamin D 70 I.U. 18 Vitamin E 7 I.U. 23 Vitamin K 20 mcg ** Vitamin C35 mg 58 Thiamine (B₁) .5 mg 33 Riboflavin (B₂) .6 mg 35 Niacin 7 mg 35Vitamin B₆ 1 mg 50 Folic Acid 135 mcg 34 Pantoth Acid 3.5 mg 35 VitaminB₁₂ 2 mcg 33 Biotin 100 mcg 33 Choline 112 mg ** Taurine 20 mg **L-Carnitine 20 mg ** Calcium 200 mg 20 Phosphorus 175 mg 18 Magnesium100 mg 25 Zinc 3.5 mg 23 Iron 3 mg 17 Copper .35 mg 18 Manganese .68 mg** Iodine 25 mcg 17 Sodium 125 mg ** Potassium 313 mg ** Chloride 250 mg** Chromium 10 mcg ** Molybdenum 30 mcg ** Selenium 10 mcg ** *% U.S.RDA Recommended daily allowance for adults and children 4 or more yearsof age **U.S. RDA not established ***Includes high amylose corn starch -70% amylose (4% of the caloric content of the product) and guar gum(0.4% of the caloric content of the product). ****MCT provides 6.75grams/250 ml

By way of example, and not limitation, experiments relating to thepresent invention are as follows:

EXPERIMENT NO. 1

Peptamen® is a hydrolyzed whey protein based enteral solution which ismanufactured by a UHT process and aseptically filled into cans andaseptic pouches. Serum separation has been observed in some Peptamen®products. The serum usually develops within 2 weeks and develops morerapidly at cooler temperatures (40° F. and 72° F.) than at elevatedtemperatures (86° F. and 100° F.).

It has been surprisingly determined that the serum separation inPeptamen® is due to thermodynamic incompatibility between the starch andthe guar gum. The purpose of this study is to demonstrate thecompatibility of the starches and gums and to determine the optimumpolysaccharide combinations for a Peptamen® type system.

Methodology:

A Peptamen® formula, based on hydrolyzed whey (see Table 1), was used asthe base for evaluation of the compatibility of the starches and gums.The starches included Melojel (low amylose starch) (25% amylose fromNational Starch) and Eurylon 7 (high amylose starch) (70% amylose fromRoquette). The gums evaluated included guar gum as well as xanthan gum(Keltrol SF). A 50:50 blend of Xanthan gum and guar gum was alsoevaluated. In addition a blend of iota and kappa carrageenans was alsoevaluated to determine its effect on serum separation.

The variables were put into storage at 40° F., 72° F., 86° F. and 100°F. conditions and were evaluated on 2 week intervals for serumseparation and viscosity change. In addition fresh samples weretransferred from the cans into sterile jars and stored at ambienttemperature for visual inspection of the samples.

TABLE NO. 1 MELOJEL LOW MELOJEL LOW EURYLON 7 HIGH AMYLOSE AMYLOSEAMYLOSE STARCH STARCH STARCH GUAR GUM/ GUAR GUM GUAR GUM CARRAGEENANINGREDIENT % % % LIQUID HYDROLYZED WHEY 38.593 38.593 38.593 MCT OIL2.630 2.630 2.630 SOYBEAN OIL 0.624 0.624 0.624 LECITHIN 0.200 0.2000.200 MALTODEXTRIN 10 DE 10.4000 10.9000 10.4000 CORN STARCH-MELOJEL1.6100 — 1.6100 CORN STARCH-EURYLON 7 — 1.1000 — GUAR GUM 0.1177 0.11770.1177 CARRAGEENAN VISCARIN — — 0.005 CARRAGEENAN SEAKEM — — 0.025POTASSIUM CITRATE TRIBASIC 0.0897 0.0897 0.0897 SODIUM CITRATE* 2H200.0250 0.0250 0.0250 POTASSIUM CHLORIDE 0.0557 0.0557 0.0557 SODIUMPHOSPHATE DIBASIC 0.0830 0.0830 0.0830 anhydrous CALCIUM CITRATE *4 H200.0603 0.0603 0.0603 TRICALCIUM PHOSPHATE 0.1193 0.1193 0.1193 MAGNESIUMCHLORIDE *6 H20 0.1280 0.1280 0.1280 MAGNESIUM OXIDE 0.0160 0.01600.0160 L-CARNITINE 0.0120 0.0120 0.0120 CHOLINE CHLORIDE 0.0660 0.06600.0660 MINERAL PREMIX 0.0430 0.0430 0.0430 BETA CAROTENE 1% 0.01300.0130 0.0130 VITAMIN PREMIX 0.1347 0.1347 0.1347 STANDARDIZATION WATER44.9796 44.9896 44.9496 100.0000 100.0000 100.0000

Results:

Effect of starch and gum combinations on serum separation and sediment:

The control samples containing Melojel starch and guar gum had serum inthe top layer as occurs in some such commercial batches. The formulascontaining Eurylon 7 starch and guar gum had the least or no serumdevelopment compared to those containing Melojel starch. The amount ofseparation was similar in the samples containing guar or xanthan gum incombination with the Melojel starch.

However, in the sample containing the blend of guar and xanthan gumswith Melojel starch the serum separation occurred at a slower rate. Thedegree of separation was still greater than in the variables containingguar gum and Eurylon 7 starch. Addition of carrageenan to the Melojelstarch/guar gum combination significantly reduced the serum separation.Formulas containing either Melojel starch or Eurylon starch without anygum had no serum separation, however salt sediment and slight serumseparation was at the bottom of the can and a significant creamseparation was evident.

The Eurylon 7 starch and guar gum formulas, which were stable, hadsimilar viscosity to their respective Melojel starch formulas which hadseparation. Therefore, it appears that the serum separation is notrelated to the product viscosity in the Peptamen® regular formula (seeTable 2 below). The viscosity however does appear to correlate withsedimentation (see FIG. 1).

Formulas without guar gum added had lower viscosity and greater saltsediment compared to formulas containing gum which had higher viscosity.The variable with Eurylon 7 starch alone had slightly smaller amount ofsediment than Melojel (low amylose) starch alone. Carrageenan added tothe Melojel starch formula increased the viscosity slightly and reducedthe sediment slightly. However, the sediment was still visible andsignificantly more than samples containing the Melojel starch and guargum.

TABLE 2 Serum and Viscosity after 3 months storage at 72° F. Serum Vis-(mls/ cos- Use Use 340 ity Code Starch Level Gum Level mls) Cp* 1363-79AMelojel 1.6% Guar 0.117 150 47 1363-80C Eurylon 7 1.1% Guar 0.117 5 441363-109B Hylon VII 1.1% Guar 0.117 5 43 1363-79C Melojel 1.6% Xanthan0.117 165 55 1363-87C Eurylon 7 1.1% Xanthan 0.117 5 55 1363-71B Melojel1.6% Guar/ 0.0525/ 70 55 Xanthan 0.0525 1363-71C Eurylon 7 1.1% Guar/0.0525/ 0 72 Xanthan 0.0525 1363-79B Melojel 1.6% None 0 20 17 1363-80AEurylon 7 1.1% None 0 5 12 1363-72C Melojel 1.6% Guar + 0.117 0 52Carrageenan 1363-87B Melojel 1.6% Carrageenan 0 20 19 only *Viscositymeasured using Brookfield LV-DV-1 Viscometer with spindle #1 at 60 rpm;Product temperature @ 70° F.

Storage at different temperatures, i.e., 40° F. and 100° F., indicatesthat Eurylon 7 starch is more stable and does not develop serum at allthe tested storage conditions as does Melojel starch. The Melojelstarch/guar gum/carrageenan variable which is stable at ambienttemperature for 3 months had some serum separation at 40° F., however itis significantly less than without the added carrageenan (50 mls vs 150mls). The viscosity of the Eurylon 7 does not change significantlyduring storage at both 72° F. and 100° F. conditions (See FIG. 2). TheEurylon 7 variables also exhibited less viscosity change at 100° F. thanthe Melojel Starch.

Conclusions:

The stability studies after 3 months indicate that in Peptamen®, highamylose starch such as Eurylon 7 and Hylon 7 (National Starch Co.) aremore compatible with guar and xanthan gums than is Melojel starch.Adding carrageenan (iota/kappa blend) to the system containing Melojelstarch and guar gum is also effective in reducing serum development.

Removing the guar gum from the formula does result in significantlyreduced serum, however resulted in sedimentation of the insoluble saltsdue the low viscosity of the product.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present invention andwithout diminishing its attended advantages. It is therefore intendedthat such changes and modifications be covered by the appended claims.

We claim:
 1. A nutritional product comprising: a protein source; a lipidsource; a carbohydrate source including high amylose starch and guargum, wherein high amylose starch and guar gum as a total compriseapproximately 2.25% to about 7.50% of the total caloric content.
 2. Anutritional product comprising: a protein source; a lipid source; and acarbohydrate source including high amylose starch and guar gum, the highamylose starch comprises approximately 2.0% to about 6.5% of the totalcaloric content.
 3. A nutritional product comprising: a protein source;a lipid source; and a carbohydrate source including high amylose starchand guar gum, the guar gum comprises 0.25% to about 1.0% of the totalcaloric content.
 4. A nutritional product comprising: a protein source;a lipid source; and a carbohydrate source including high amylose starchand guar gum, the high amylose starch comprises at least approximately50% by weight amylose.
 5. A nutritional product comprising: a proteinsource; a lipid source; and a carbohydrate source including high amylosestarch and guar gum, the weight ratio of high amylose starch to guar gumis approximately 2.5:1 to 16:1.
 6. The nutritional product of claim 1including carrageenan.
 7. The nutritional product of claim 1 wherein thecarbohydrate source comprises approximately 40 to about 60% of thecaloric content.
 8. The nutritional product of claim 1 wherein theproduct is designed to be an enteral product.
 9. The nutritional productof claim 1 including xanthan.
 10. A nutritional product of comprising: ahydrolyzed whey protein source; a source of lipids; a sufficient amountof a stabilizer to reduce serum separation, the stabilizer includinghigh amylose starch and guar gum, wherein high amylose starch and guargum as a total comprise approximately 2.25% to about 7.5% of the totalcaloric content.
 11. A nutritional product comprising: a hydrolyzed wheyprotein source; a source of lipids; and a sufficient amount of astabilizer to reduce serum separation, the stabilizer including highamylose starch and guar gum, the high amylose starch comprisesapproximately 2.0% to about 6.5% of the total caloric content.
 12. Anutritional product comprising: a hydrolyzed whey protein source; asource of lipids; and a sufficient amount of a stabilizer to reduceserum separation, the stabilizer including high amylose starch and guargum, the guar gum comprises 0.25% to about 1.0% of the total caloriccontent.
 13. A nutritional product comprising: a hydrolyzed whey proteinsource; a source of lipids; and a sufficient amount of a stabilizer toreduce serum separation, the stabilizer including high amylose starchand guar gum, the weight ratio of high amylose starch to guar gum isapproximately 2.5:1 to 16:1.
 14. A nutritional product comprising: ahydrolyzed whey protein source; a source of lipids; a sufficient amountof a stabilizer to reduce serum separation, the stabilizer includinghigh amylose starch and guar gum; and at 1500 Kcals at least 100% of theU.S. RDA of vitamins and minerals.
 15. The nutritional product of claim10 wherein the product includes carrageenan.
 16. The nutritional productof claim 10 wherein the carbohydrate source comprises approximately 40to about 60% of the caloric content.
 17. A nutritional productcomprising: a hydrolyzed whey protein source; a source of lipids; and asufficient amount of a stabilizer to reduce serum separation, thestabilizer including high amylose starch and guar gum, the high amylosestarch comprising at least approximately 50% amylose.
 18. Thenutritional product of claim 10 wherein the product is designed to be anenteral product.
 19. The nutritional product of claim 10 includingxanthan.
 20. A method of stabilizing an enteral solution comprising thesteps of adding to an enteral solution a stabilizing amount of highamylose starch and guar gum, wherein high amylose starch and guar gum asa total comprise approximately 2.25% to about 7.50% of the total caloriccontent.
 21. A method of stabilizing an enteral solution comprising thesteps of adding to an enteral solution a stabilizing amount of highamylose starch and guar gum, wherein high amylose starch comprisesapproximately 2.0% to about 6.5% of the total caloric content.
 22. Amethod of stabilizing an enteral solution comprising the steps of addingto an enteral solution a stabilizing amount of high amylose starch andguar gum, the guar gum comprises 0.25% to about 1.0% of the totalcaloric content.
 23. A method of stabilizing an enteral solutioncomprising the steps of adding to an enteral solution a stabilizingamount of high amylose starch and guar gum, the high amylose starchcomprises at least approximately 50% by weight amylose.